Clinical implications of nonsarcomeric gene polymorphisms in hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is characterized by cardiomyocyte hypertrophy and fibrosis. Although is an autosomal dominant trait, a group of nonsarcomeric genes have been postulated as modifiers of the phenotypic heterogeneity. MATERIAL AND METHODS: We prospectively recruited 168 HCM patients and 136 healthy controls from three referral centres. Patients and controls were clinically stable at entry in the study. Nine polymorphisms previously associated with ventricular remodelling were determined: I/D ACE, AGTR1(A1666C), CYP11B2(C344T), PGC1-α(G482S), COLIA1(G2046T), ADRB1(R389G), NOS3(G894T), RETN(-420C>G) and CALM3(-34T>A). Their potential influence on prognosis, assessed by hospital admissions, and their cause were recorded. RESULTS: The median follow-up time was 49·5 months. Allele and genotype frequencies did not differ between patients and controls. Thirty-six patients (21·5%) required urgent hospitalization (18·5% for heart failure, 22·2% for atrial arrhythmias, 11·1% for ventricular arrhythmias, 29·6% for ischaemic heart disease, 14·8% for stroke and 3·7% for other reasons) with a hospitalization rate of 8·75% per year. Multivariate analysis showed an independent predictive value for noncarriers of polymorphic COL1A1 allele [HR: 2·76(1·26-6·05), P = 0·011] and a trend in homozygous carriers of ADRB1 Arg389 variant [HR: 1·98(0·99-4·02); P = 0·057]. CONCLUSION: Our study suggests that COL1A1 polymorphism (2046G>T) is an independent predictor of prognosis in HCM patients supporting the importance of nonsarcomeric genes on clinical prognosis in HCM.

Cardiac resynchronization therapy: do patient selection and implant practice vary depending on the volume a center handles?

BACKGROUND: The annual volume of implants may condition and determine many aspects of cardiac resynchronization therapy (CRT). METHODS: After the Spanish centers performing CRT were identified, data were recorded voluntarily by each implantation team from September 2010 to September 2011. RESULT: A total of 88 implanter centers were identified, and of these 85 (96.5%) answered the questionnaire. In total, 2,147 device implantations were reported, comprising 85% of the Eucomed's overall estimate for the same period, which was 2,518 implantations. Centers handling a higher volume of implants have a higher percentage of patients referred from other centers and more indications in patients over 80 years of age, with atrial fibrillation (AF), right bundle branch block, and unspecific disorders of intraventricular conduction. These high-volume centers stimulate more frequently in patients with very wide QRS > 200 ms. Lower-volume centers select more classic patients for resynchronization, whereas higher-volume centers increase the rate of patients with AF and prior cardiac stimulation (upgrade). Implant duration is shorter for higher-volume centers, which also perform implants in patients with congenital heart disease. By contrast, there are no significant differences in terms of heart disease, device type (pacemaker or defibrillator), implant techniques, achieved optimal site location, or complications. CONCLUSIONS: High-volume centers perform CRT more frequently in elderly patients, mostly with AF and other alternative implants. No significant differences were found between the complications reported by high-volume centers and those reported by low-volume centers.

Health-related quality of life in different clinical subgroups with typical AFL who have undergone cavo-tricuspid isthmus ablation.

BACKGROUND: To evaluate changes in health-related quality of life (HRQOL) in different sub-groups of a cohort of patients with typical atrial flutter (AFL) treated with cavotricuspid isthmus (CTI) radiofrequency catheter ablation. METHODS: 95 consecutive patients due to undergo CTI ablation were enrolled in a study involving their completion of two SF-36 HRQOL questionnaires, before ablation and at one-year follow-up. RESULTS: 88 of the initial 95 patients finished the study. Regardless of whether patients experienced atrial fibrillation (AF) during follow-up, a statistically significant improvement in HRQOL was observed, compared with pre-ablation scores and in all dimensions except Bodily Pain. However, patients without AF during follow-up had significantly higher absolute HRQOL scores in most dimensions. No differences were seen in most HRQOL dimensions, with respect to AFL type (paroxysmal, persistent) or duration, whether AFL was first-episode or recurrent, Class I-III drug dependent, sex, or presence of structural heart disease or tachycardiomyopathy. Patients with persistent AFL showed the greatest improvement in HRQOL when they also had a ventricular cycle length ≤500 ms. The combination of recurrent AFL, ventricular cycle length ≤500 ms and structural heart disease led to a significantly greater improvement in physical HRQOL dimensions than did first-episode AFL, no structural heart disease and ventricular cycle >500 ms. The only independent factor associated with a greater improvement was structural cardiopathy. CONCLUSIONS: CTI-ablation treatment leads to a significant improvement in HRQOL in patients with typical AFL. Patients with AF during follow-up show a significantly lower HRQOL at one-year post-ablation. The only independent risk factor found to be associated with a greater improvement in the physical summary component was structural cardiopathy.

Non-antiarrhythmic drugs to prevent atrial fibrillation.

Atrial fibrillation (AF) is the most frequent arrhythmia found in clinical practice. The majority of patients with AF are still candidates for antiarrhythmic drug treatment, not only for acute reversion to sinus rhythm but also for long-term treatment to prevent recurrences of AF. Currently available antiarrhythmic drugs, however, are unable to provide complete efficacy in all patients, and present problematic risks of proarrhythmia. The progressively increasing prevalence of AF supports the need to develop improved therapeutic approaches for the clinical management of arrhythmia. Accordingly, new treatment techniques aimed at suppressing the origin of the arrhythmogenic foci have been developed in the last decade. However, ablative treatments are only available for selected patients. Because of these factors, and also because primary prevention of AF should be our goal, the introduction of non-antiarrhythmic agents that could prevent both new-onset AF and recurrences of AF may eventually improve patient outcomes and reduce the incidence of this epidemic disease. The potential clinical value of these non-antiarrhythmic options is currently under active investigation. There is now clinical and experimental evidence that many drugs may have beneficial effects in preventing AF through several possible mechanisms. Non-antiarrhythmic drugs, such as ACE inhibitors and angiotensin receptor blockers, HMG-CoA reductase inhibitors (statins), corticosteroids, and N-3 polyunsaturated fatty acids may have a positive effect in patients with AF or in preventing AF in patients at risk.

[Cardiac arrhythmias in women]. / Arritmias cardiacas en la mujer.

The aim of this study was to review published data on gender differences in cardiac electrophysiology and in the presentation and clinical treatment of arrhythmias. The evidence from studies published to date show that women have a higher mean resting heart rate, a longer QT interval, a shorter QRS duration, and a lower QRS voltage than men. Women have a higher prevalence of sick sinus syndrome, inappropriate sinus tachycardia, atrioventricular nodal reentry tachycardia, idiopathic right ventricular tachycardia, and arrhythmic events in the long-QT syndrome. In contrast, men have a higher prevalence of atrioventricular block, carotid sinus syndrome, atrial fibrillation, supraventricular tachycardia due to accessory pathways, Wolff-Parkinson-White syndrome, reentrant ventricular tachycardia, ventricular fibrillation and sudden death, and the Brugada syndrome. With regard to implantable devices, it has been reported that defibrillators offer similar benefits in men and women. Moreover, there is no gender difference in the percentage who respond well to resynchronization therapy: survival is similar in the two sexes. However, it should be noted that few women have participated in studies of all types of therapy, including catheter ablation, resynchronization therapy, and the use of implantable defibrillators.

Use of irbesartan to maintain sinus rhythm in patients with long-lasting persistent atrial fibrillation: a prospective and randomized study.

BACKGROUND: Data from studies of angiotensin-converting enzyme inhibitors provide evidence that the renin-angiotensin-aldosterone system plays a role as a mediator of atrial remodeling in atrial fibrillation. The present study has evaluated the effect of treatment with the angiotensin I type 1 receptor blocker irbesartan on maintaining sinus rhythm after conversion from persistent atrial fibrillation. METHODS AND RESULTS: To be included in the present study, patients must have had an episode of persistent atrial fibrillation for >7 days. The patients were then randomized and scheduled for electrical cardioversion. Two groups of patients were compared: Group I was treated with amiodarone, and group II was treated with amiodarone plus irbesartan. The primary end point was the length of time to a first recurrence of atrial fibrillation. From a total of 186 patients assessed in the study, 154 were analyzed with the use of intention-to-treat analysis. Seventy-five patients were randomly allocated to group I and 79 to group II. After 2 months of follow-up in the intention-to-treat analysis, the group treated with irbesartan had fewer patients with recurrent atrial fibrillation (Kaplan-Meier analysis, 84.79% versus 63.16%, P=0.008). The Kaplan-Meier analysis of time to first recurrence during the follow-up period (median time, 254 days [range, 60 to 710]) also showed that patients treated with irbesartan had a greater probability of remaining free of atrial fibrillation (79.52% versus 55.91%, P=0.007). CONCLUSIONS: Patients treated with amiodarone plus irbesartan had a lower rate of recurrence of atrial fibrillation than did patients treated with amiodarone alone.

[Multiple pulmonary nodules and amiodarone. KL-6 as a new diagnostic tool]. / Nódulos pulmonares múltiples y amiodarona. KL-6 como nueva herramienta diagnóstica.

Pulmonary toxicity is an infrequent but serious adverse event in patients treated with amiodarone. The main problem at present is that we lack the necessary tools to detect this event or predict which patients will develop pulmonary toxicity. Serum Krebs von den Lungen-6 (KL-6) has been previously recognized as a marker for the activity of diffuse interstitial lung disease. We describe a patient with pulmonary toxicity due to amiodarone with increased blood levels of this new marker, and discuss the clinical usefulness of this new diagnostic tool.

Prevention of recurrences in patients with lone atrial fibrillation. The dose-dependent effect of angiotensin II receptor blockers.

BACKGROUND: Atrial fibrillation (AF) leads to the activation of the renin-angiotensin system (RAS), which seems to play an important role in atrial remodelling. It is not known yet whether RAS blockade may prevent recurrences in patients with lone AF. METHODS AND RESULTS: Patients with an episode of persistent AF for >7 days, in the absence of cardiac or extracardiac causes and with normal blood pressure values (lone AF), were recruited. Ninety patients were randomised and scheduled for electrical cardioversion. Three groups of patients were compared: Group I was treated with amiodarone 400 mg daily (30 patients), group II was treated with amiodarone 400 mg daily plus irbesartan 150 mg daily (30 patients) and group III with amiodarone 400 mg daily plus irbesartan 300 mg daily (30 patients). The primary endpoint was the time to a first recurrence of AF. The patients were cardioverted and followed. The Kaplan-Meier analysis of time to first recurrence during the follow-up period showed that patients treated with amiodarone 400 mg plus irbesartan 300 mg had a greater probability of remaining free of AF (77% vs. 52% for amiodarone and 65% for amiodarone+irbesartan 150 mg), hazard ratio for a recurrence in group III: 0.47 (95% CI 0.27-0.82; p=0.001). CONCLUSIONS: The combination of irbesartan plus amiodarone decreased the rate of AF recurrences, with a dose-dependent effect, in lone AF patients.

[Cardiac resynchronization for heart failure: background, methods, indications and results]. / Resincronización cardíaca en la insuficiencia cardíaca: bases, métodos, indicaciones y resultados.

Heart failure is one of the most prevalent diseases in industrialized countries. Although the prognosis of patients with heart failure is still poor, in recent decades new therapies have been investigated in order to improve quality of life and survival. However, up to 30% of the patients with advanced heart failure present disturbances in intraventricular conduction, and this produces asynchrony of ventricular contractility, leading to further deterioration in heart function. Cardiac resynchronization therapy can improve the synchrony of ventricular contractility. Numerous studies have demonstrated the benefits of biventricular stimulation therapy for improving hemodynamic parameters, quality of life, 6-minute walking test performance and functional class in patients with heart failure, ventricular systolic dysfunction and disturbances in intraventricular conduction. Some studies have demonstrated longer survival times in patients treated with cardiac resynchronization plus a defibrillator. Nonetheless, many questions about the benefits of heart resynchronization therapy, site of stimulation and best type of device (pacemaker or defibrillator) remain unresolved.

[Ablation of the cavotricuspid isthmus. Randomized prospective study of radiofrequency ablation with irrigated catheters versus standard catheters]. / Ablación del istmo cavotricuspídeo. Estudio prospectivo aleatorizado sobre ablación mediante radiofrecuencia con catéteres irrigados frente a catéteres estándar.

INTRODUCTION AND OBJECTIVES: An important limitation of the ablation with standard catheter is the volume and limited depth of the lesions created. The irrigated catheters, due to a larger and deeper lesion could be useful in patients with typical atrial flutter. The aim of this study was to prospectively compare the ablation procedure with an irrigated-tip catheter versus the standard catheter in this group of patients. METHODS: A total of 37 consecutive patients referred to ablation of the cavotricuspid isthmus for typical atrial flutter were randomized either to be performed by an standard catheter (20 patients with mean age of 62 18 years, 18 males) or an irrigated-tip catheter (17 patients with mean age 71 4 years, 13 males). RESULTS: With standard catheters, complete ablation of the cavotricuspid isthmus was achieved in 18 patients (90%). With a mean of 19 15 applications. With the irrigated-tip catheters the complete ablation of the isthmus was achieved with a mean of 8 7 applications (p < 0.001). Both mean duration of the procedure (164 56 versus 70 35 minutes) and fluoroscopic time (40 16 versus 16 8 minutes) was significantly less with irrigated catheters (p < 0.001). There were no significant clinical complications during the procedure nor later on. No patient presented ischemic symptoms nor alterations on the ST segment. CONCLUSIONS: The employment of irrigated-tip catheters achieved a high success rate with safety shortening the procedure time and radiation exposure.

[External and internal electrical cardioversion: comparative, prospective evaluation of cell damage by means of troponin I]. / Cardioversión eléctrica externa y sistemas de cardioversión interna: evaluación prospectiva y comparativa del daño celular con troponina I.

INTRODUCTION AND OBJECTIVES: In this study we measured the concentrations of cardiac troponin I (cTnI) and several biochemical markers of myocardial damage after elective external cardioversion or internal cardioversion by specific catheters or automatic defibrillators. MATERIAL AND METHODS: Biochemical markers were analyzed prospectively for 30 consecutive patients after electrical cardioversion. Concentrations of cTnI, myoglobin, creatine kinase (CK), CK-MB and the MB/CK ratio were determined in samples before cardioversion and 2, 8 and 24 h later. The shock energy ranged from 50 to 360 joules (235 106 joules) in external cardioversions and from 3 to 37 joules (15 8 joules) in internal cardioversions. RESULTS: We detected abnormal concentrations of CK, myoglobin, CK-MB and MB/CK in 33% of the patients after external cardioversion. The concentrations of cTnI remained within normal limits at all times, with no elevations detected. Whereas no abnormal concentration of any biochemical marker was detected in any patient who required internal cardioversion for atrial fibrillation, two patients who underwent external cardioversion from an automatic defibrillator did have abnormal concentrations of CK-MB, myoglobin, and even of cTnI. CONCLUSIONS: The concentration of cTnI remained below the detection limit after external cardioversion, even though the other more non-specific markers changed. No enzyme alteration was detected in patients who underwent internal cardioversion of atrial fibrillation.

[Lesions produced by radiofrequency ablation of the cavotricuspid isthmus in an experimental model]. / Lesiones producidas por la ablación con radiofrecuencia del istmo cavotricuspídeo en un modela experimental.

INTRODUCTION AND OBJECTIVES: Experimental studies have shown that deeper and wider lesions (up to 10 mm long or deep) can be safely created using an 8 mm or irrigated tip catheter for ablation to treat atrial flutter. However, potential damage to the tricuspid valve or inferior cava vein has not been systematically evaluated. PATIENTS AND METHOD: The cavotricuspid isthmus was ablated in 26 pigs (body weight 26-52 kg), with a total of 187 radiofrequency pulses. Standard 4 mm, 8 mm and irrigated tip catheters were used at random. For each ablation, energy, impedance and temperature were recorded continuously. RESULTS: The lesions were larger with irrigated tip and 8-mm catheters than with standard ones. In 7 animals (1 with an irrigated tip, 4 with an 8-mm, and 2 with a standard tip) the tricuspid valve was damaged. The tricuspid valve was severely damaged in 3 pigs and lesions were moderate in 4. In animals with tricuspid valve lesions, maximal energy was higher (59 +/- 27 vs. 51 +/- 24 W; p=0,03) and higher temperatures were reached (63 +/- 4 vs. 55 +/- 11 degrees C; p<0.001). Low energy pulses measured before ablation were also more intense in animals in which damage was produced (0.55 +/- 0.24 vs. 0.35 +/- 0.29; p=0.001), indicating greater contact pressure. CONCLUSIONS: The tricuspid valve may be severely damaged during the ablation of the cavotricuspid isthmus for atrial flutter: damage was seen most often with high energy pulses and with 8-mm catheters, but can also occur with usual energy levels and standard catheters. To minimize damage this technique should not be used from the inside of the right ventricle just above the tricuspid valve.

[Usefulness of brain natriuretic peptide to evaluate patients with heart failure treated with cardiac resynchronization]. / Utilidad del péptido natriurético BNP en la evaluación de pacientes con insuficiencia cardíca tratados con resincronización cardíaca.

INTRODUCTION AND OBJECTIVES: The aim of the present study was to document the evolution of the blood levels of brain natriuretic peptide (BNP) in patients with heart failure and their correlation with the clinical course after implantation of a biventricular pacemaker. PATIENTS AND METHOD: Twenty-eight patients with heart failure associated to left bundle branch block and left ventricular systolic dysfunction were included in the study. In each patient we performed laboratory tests, chest X-ray, electrocardiogram and echocardiogram, and measured blood levels of BNP. RESULTS: During follow-up (10 [6] months) functional capacity improved, decreasing from 3.3 (0.6) to 2.10 (0.4) (P=.03). The rate of hospitalizations for heart failure decreased from an average of 1.8 (0.7) (6 months before the procedure) to 0.8 (0.3) (6 months after the procedure; P=.04). The basal value of BNP decreased from 193 (98) pg/mL to 52 (14) at the end of the follow-up in the responder group (22 patients) and increased from 564 (380) to 650 (80) pg/mL in the nonresponder group (6 patients). Patients who responded showed significant clinical improvement and decreasing levels of BNP, which reached a plateau an average of 6 months after implantation. Multivariate logistic regression analysis identified lower levels of BNP, idiopathic dilated cardiomyopathy, and functional class as independent predictors of response to therapy. Age, QRS width and left ventricular ejection fraction were not predictors of response. CONCLUSIONS: Brain natriuretic peptide concentrations allowed us to monitor, in an objective manner, the clinical course of patients with biventricular resynchronization therapy.

Cross-sectional study of cardiac resynchronization therapy in Spain. Indications, implant techniques, optimization and follow-up.

INTRODUCTION AND OBJECTIVES: A cross-sectional study of cardiac resynchronization therapy use in Spain was performed to analyze problems with indications, implantation, and patient follow-up. METHODS: Spanish cardiac resynchronization therapy implanter centers were identified, then the department members were surveyed and the data were recorded by each implantation team. RESULTS: Eighty-eight implanter centers were identified; of these, 85 (96.6%) answered the survey. A total of 2147 device implantations were reported, comprising 85.6% of the overall number of 2518 implantations estimated by the European Confederation of Medical Suppliers Associations for the same period. The reported implantation rate was 46 per million inhabitants versus an estimated implantation rate of 51 per million (European average, 131). Cardiac resynchronization therapy devices accounted for 84% of implantations, and upgrades to previously implanted devices, 16%. The majority of cardiac resynchronization therapy devices were implanted in men (70.7%). The mean age was 68 (12) years, and the mean left ventricular ejection fraction was 26.4% (5%). Most patients (67%) were in New York Heart Association functional class III. The group of patients for whom cardiac resynchronization therapy was indicated according to the latest update of the guidelines was significant: 17.3% among New York Heart Association class II patients and more than 21.6% among patients with atrial fibrillation. In all, electrophysiologists accounted for 73.8% of implanters, followed by surgeons, accounting for 21.4%. CONCLUSIONS: The latest update of the guidelines is being progressively implemented in Spain, according to data obtained in patients in New York Heart Association class II or with atrial fibrillation. Nevertheless, the number of cardiac resynchronization therapy device implants is still well below the European average.

[Progress in cardiac electrophysiology and arrhythmias]. / Novedades en electrofisiología cardiaca y arritmias.

This article provides a commentary on some of the most significant research on cardiac arrhythmias published during the last year. Publications were selected for their clinical importance or because they report on improvements in the invasive techniques used in cardiac electrophysiology.

Selecting the best site for pacing leads after cardiac surgery by evaluating the asynchrony of myocardial deformation observed with different pacing sites.

INTRODUCTION AND OBJECTIVES: After cardiac surgery, temporary pacing leads are routinely implanted in the right ventricle (RV). The objective was to investigate the effect of different ventricular pacing locations on cardiac synchrony (by evaluating myocardial deformation, or strain) and efficiency in patients undergoing cardiac surgery. METHODS: Interventricular asynchrony (i.e. the difference in the time of onset of deformation between right and left ventricles; Tε-R/L) and intraventricular asynchrony (i.e. the standard deviation and maximum difference in the time of onset of deformation in six segments of the left ventricle [LV]; Tε-SD and Tε-MD, respectively) were assessed in 19 patients. Doppler echocardiography was used to evaluate these parameters and cardiac output after pacing in the RV and in three different LV segments. RESULTS: Pacing in the RV resulted in the greatest increases in asynchrony parameters from baseline: Tε-R/L 59.8 ms (standard deviation [SD] 40.5 ms) vs. 28.23 ms (SD 56.9 ms), P=.002; Tε-SD 53.2 ms (SD 34.4 ms) vs. 36.6 ms (SD 34.9 ms), P=.007; and Tε-MD 135.3 ms (SD 82.9 ms) vs. 90.5 ms (SD 87.4 ms), P=.007. Pacing in the LV resulted in less asynchrony: for anterior LV pacing, Tε-R/L was 17.2 ms (SD 53.8 ms), Tε-SD was 35.8 ms (SD 17.9 ms), and Tε-MD was 91.3 ms (SD 45.2). The change from baseline was not significant. Cardiac output was lower after RV pacing than after anterior LV pacing: 4.36 (SD 1) vs. 4.70 (SD 1); P=.001. CONCLUSIONS: Pacing in the LV produced less asynchrony than RV pacing. In addition, anterior LV pacing resulted in a higher cardiac output than RV pacing. These findings suggest that the location normally used for temporary leads after cardiac surgery should be changed.